Assessment of the Use of NMR Chemical Shifts as Replica-Averaged Structural Restraints in Molecular Dynamics Simulations to Characterize the Dynamics of Proteins

It has been recently proposed that NMR chemical shifts can be used as replica-averaged structural restraints in molecular dynamics simulations to determine the conformational fluctuations of proteins. In this work, we assess the accuracy of this approach by considering its application to the case of ribonuclease A. We found that the agreement between experimental and calculated chemical shifts improves on average when the chemical shifts are used as replica-averaged restraints with respect to the cases in which X-ray structures or ensembles of structures obtained by standard molecular dynamics simulations are considered. These results indicate that the use of chemical shifts as structural restraints enables a bias of the conformational sampling to be introduced in a system-specific manner to reproduce accurately the conformational fluctuations of proteins.